Lessons learned from targeting eosinophils in human disease

Eosinophils are a minor subset of the granulocyte lineage distinguished by their unique morphology, phenotype, cytoplasmic contents, and function. Evolutionarily, these are ancient cells whose existence has been conserved within vertebrates for millions of years, suggesting that their contribution to innate immunity and other pathologic and homeostatic responses are important to the host. Knowledge regarding the role of eosinophils in health and disease took a leap forward in 2004 with the creation of mouse strains deficient in eosinophils. This advance was paralleled in humans using pharmacology, namely, with the development of drugs capable of selectively reducing and sometimes even eliminating human eosinophils in those receiving these agents. As a result, a more definitive picture of what eosinophils do, and do not do, is emerging. This review will summarize recent advances in our understanding of the role of eosinophils in human disease by focusing mainly on data from clinical studies with anti-eosinophil therapies, even though the first of such agents, mepolizumab, was only approved in the USA in November 2015. Information regarding both efficacy and safety will be highlighted, and where relevant, intriguing data from animal models will also be mentioned, especially if there are conflicting effects seen in humans.